MIMICS-2 Study: 1-Year Results US, German and Japanese

Experience with theBioMimics 3D Stent

Thomas Zeller, MDOn behalf of the MIMICS-2 Investigators

PAM XXX Issue 01“CAUTION: Investigational Device. Limited by Federal (or United States) Law to Investigational Use”.

Disclosure

Speaker name: Thomas Zeller

.................................................................................

I have the following potential conflicts of interest to report:

X Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

MIMICS Clinical Program

FIHN=101 site

Feasibility

Mimics RCT

RandomizedControlled Trial*

vs. straight stent

N=508 sites2-Yr follow-up

CE Mark

MIMICS-2

Prospective, Multinational Interventional Study

N=27143 sites36-monthfollow-up

IDE Study (US, Japan, Germany)

MIMICS-3D

Prospective, MultinationalObservational Registry

Non-selected patients

N=500+25 sites36-monthfollow-up

EuropeanPostmarketSurveillance

MIMICS et seq

Investigator-initiated, prospective and retrospective studies

N = c.50020+ sites

PostmarketSurveillance & Geographic Expansion

* Zeller et al Circ Cardiovasc Interv. 2016

Extending BioMimics 3D Stent evaluation to more than 1,250 subjects in 100+ sites

Natural Swirling Flow may be compromised by anatomy, disease and straight stents

Protective

Suboptimal

Pathogenic

1.5

0.5

7.0

Wall Shear Stress

(Pascal)

Malek et al JAMA 1999

Straight Stent 3D Helical Stent Porcine common carotid arteries(N=10 animals)

At 30 days:45% less intimal hyperplasia in the helical stents1

(p < 0.005)

Swirling Flow: Hypothesis for Stent Improvement

1. Caro et al., 2013

Mimics RCT: Proof of Principle

BioMimics 3D (N=50)

Control stent(N=26)

P value

Lesion Location Mid-Distal SFA 16% 8% 0.48Distal SFA 66% 46% 0.14

Distal SFA / Prox PA 8% 23% 0.08TASC II A 42% 42% 1.00

B 56% 58% 1.00C 2% 0% 1.00

Lesion Length mm 66 ± 29 63 ± 28 0.66Stent Length mm 99 ± 30 88 ± 22 0.08Occlusion Total 44% 46% 1.00Calcification Moderate to Severe 52% 58% 0.81

Comparison with Other Studies

ZILVER PTX IN.PACT LEVANT 2 Mimics RCT

Total Occlusions 30% 25.8% 20.6% 44%

Calcium (severe) 37% 8% 17.6% 42%

Zeller et al Circ Cardiovasc Interv. 2016

Kaplan Meier Estimate of Survival from Loss of Patency

PSVR >2.0, or >50% diameter stenosis, or adjudicated, clinically-driven TLR

Mimics RCT: Primary Patency

Log rank test

P < 0.05

80%72%

71%

55%

Months 246 12

0

20

40

60

80

100

Cu

mu

lative

Su

rviv

al

Zeller et al Circ Cardiovasc Interv. 2016

___ BioMimics 3D___ Control Stent

24 Months12

0

20

40

60

80

100

Cu

mu

lative

Su

rviv

al

Log rank

test

P = 0.03

Kaplan Meier Estimate of Survival from CDTLR (Landmark Analysis)

(Clinically-driven TLR determined through Event Adjudication)

Mimics RCT: Durable Benefit

___ BioMimics 3D

- - Control Stent

Zeller et al Circ Cardiovasc Interv. 2016

Mimics RCT:

• Better primary patency and reduced need for re-intervention through Year 2 than a straight nitinol stent

• Core lab confirmed 0% stent fracture at 2-year X-ray review

MIMICS-2

1st Presentation of One-Year Results

MIMICS-2 Study:Evaluation of Safety and Effectiveness of the BioMimics 3D Stent System in the Femoropopliteal Arteries of Patients with Symptomatic Peripheral Arterial Disease

• Primary Endpoints

• Safety: composite of death, major amputation or CDTLR through 30 days • Effectiveness: primary patency at 12-months

• Follow-up: 3 years

• 43 investigational sites enrolled 271 subjects

• US: 31 sites N = 162• Germany: 6 sites N = 78• Japan: 6 sites N = 31

• Study Principal Investigators

• Timothy M. Sullivan, MD Minneapolis, MN, USA• Thomas Zeller, MD Bad Krozingen, Germany• Masato Nakamura, MD Tokyo, Japan

• Core laboratories: ultrasound; angiography; X-ray• Clinical Event Committee (CEC) adjudication

N= 271 Subjects

Age Mean years ± SD (N) 68.4 ± 9.5 (271/271)Gender Male / Female 180 (66.4%) / 91 (33.6%)Risk Factors Diabetes Mellitus 45.4% (123/271)

Hypertension 90.0% (244/271)Hypercholesterolemia 81.9% (222/271)

Smoker Current / Former 80.8% (219/271)Coronary Revascularization Previous Percutaneous or

Surgical 43.2% (117/271)

Previous Peripheral Intervention None in target vessel 98.2% (266/271)Rutherford Category 1 0% (0/271)

2 26.9% (73/271)3 67.5% (183/271)4 5.2% (14/271)5 0.4% (1/271)

Ankle Brachial Index Mean ± SD (N) 0.70 ± 0.20 (257/271)

MIMICS-2 StudyBaseline Patient Demographics

MIMICS-2 StudyBaseline Angiography and QVA

Core Laboratory Data N= 271 Subjects

Reference Vessel Diameter (mm) Mean ± SD 5.2 ± 0.9 (269/271)Lesion Type1 De novo 100% (271/271)Lesion Location in Femoropopliteal Artery Prox 11.5% (31/270)

Mid 48.1% (130/270)Distal 40.4% (109/270)

Diameter Stenosis (%) Mean ± SD 77.8 ± 18.3 (269/271)Lesion Length (mm) Mean ± SD 81.2 ± 38.4 (269/271)Total Occlusion (%) 30.0 (81/270)Calcification (%) None - Mild 54.1 (146/270)

Moderate - Severe 45.9 (124/270)Run-off (%)- 1 or more patent tibial artery (<50% stenosis)

98.8 (237/240)

1 Investigator-reported

MIMICS-2 StudyIndex Procedure Data

N= 271 SubjectsBioMimics 3D Stents placed1 # Stents / N 305 / 271

# Subjects with 1 stent 87.5% (237/271)# Subjects with 2 stents 12.5% (34/271)

Stented Segment Length2 Mean ± SD (mm) 112.3 ± 36.3 (269/271)Diameter Stenosis2 Pre-stent % ± SD 78.8 ± 18.3 (269/271)

Post-stent % ± SD 12.6 ± 7.5 (269/271)Dissections2 No Dissection 97.8% (263/269)

Type A-C 2.2% (6/269)Type D-F 0% (0/269)

Device Success1 100% (271/271)Technical Success2 100% (269/269)

Device Success: Successful delivery of System; placement of stent and retrieval of SystemTechnical Success: Core Lab determined ≤50% residual diameter stenosis (in-stent) at end of index procedure

1 Investigator-reported2 Core Lab

MIMICS-2 StudyEndpoint: Safety

Performance Goal Rate (n/N) [95% CI]

Freedom from MAE through 30 days

>88% 99.6% (268/269) [97.7%, 100%]

Primary safety endpoint Achieved

n/N for Intention to Treat subjects: (n) 1 Subject had CDTLR Day 3 due to abrupt closure of treated segment; (N) 2 Subjects were lost to follow-up without reported MAE and without ascertainment of status past lower visit window threshold of 23 days

Confidence interval [CI] calculated by Agresti-Coull method. Lower bound corresponds to lower 97.5% one-sided Agresti-Coull interval

CDTLR: Clinically-driven target lesion revascularization is revascularization of the target lesion with objective evidence of recurrent symptoms associated with an angiographic determination of ≥50% stenosis and new distal ischemic signs (worsening ABI or worsening Rutherford Category associated with the index limb); or ≥70% angiographic diameter stenosis in the absence of objective evidence of recurrent symptoms.

Primary safety endpoint is a composite of CEC-adjudicated Major Adverse Events through 30 days, including death, any major amputation performed on the target limb, or CDTLR

MIMICS-2 IDE StudyKaplan-Meier Survival Analysis

12-Month Freedom fromCDTLR: 88.4%

Time (days) 0-0 1-30 31-60 61-120 121-180 181-240 241-300 301-365

# at risk 271 266 261 257 252 244 236 224

# subjects with events 0 1 0 2 4 8 8 7

# censored 0 4 5 2 1 0 0 5

Event-free % (cumulative) 100% 99.6% 96.6% 98.9% 97.3% 94.2% 91.1% 88.4%

SE 0.0% 0.4% 0.4% 0.7% 1.0% 1.4% 1.8% 2.0%

MIMICS-2 IDE StudyKaplan-Meier Survival Analysis

12-Month Freedom fromLoss of Primary Patency: 81.9%

Time (days) 0-0 1-30 31-60 61-120 121-180 181-240 241-300 301-360 361-365

# at risk 271 258 248 244 240 231 221 202 199

# subjects with events 0 3 0 3 4 9 10 13 3

# censored 0 10 10 1 0 0 0 6 0

Event-free % (cumulative) 100% 98.9% 98.9% 97.7% 96.1% 92.5% 88.5% 83.1% 81.9%

SE 0.0% 0.6% 0.6% 0.9% 1.2% 1.7% 2.0% 2.4% 2.4

Conclusions

• MIMICS-2 Primary Safety and Effectiveness Endpoints were met

• Probability of freedom from loss of primary patency at 12 months with BioMimics 3D is similar to those for DES/DCB

– Natural Swirling Flow is an alternative to antiproliferative drugs

• Core-lab confirmed 0% stent fracture: Mimics RCT and MIMICS-2

• Unique BioMimics 3D stent design provides hemodynamic and biomechanical benefits for primary and complementary stenting

MIMICS-2 Study: 1-Year Results US, German and Japanese

Experience with theBioMimics 3D Stent

Thomas Zeller, MDOn behalf of the MIMICS-2 Investigators

PAM XXX Issue 01“CAUTION: Investigational Device. Limited by Federal (or United States) Law to Investigational Use”.